Indanylamine and aminotetralin derivative compounds, such as those of Formula I below, are useful to treat depression, Attention Deficit Disorder (ADD), Attention Deficit and Hyperactivity Disorder (ADHD), Tourett's Syndrome, Alzheimer's Disease and other dementias as described in PCT application publication 98/27055. The indanylamine derivatives disclosed have been shown to have biological effects in animal models of neurological disease.
Formula I is:
wherein b is 1 or 2; m is from 0-3, Y is O or S, X is halo, R4 is hydrogen or C1-4 alkyl, R5 is hydrogen, C1-4 alkyl, or optionally substituted propargyl and R6 and R7 are each independently hydrogen, C1-8 alkyl, C6-12 aryl, C6-12 aralkyl, each optionally halo substituted.
PCT application publication 98/27055 further discloses methods for the preparation of indanylamine and aminotetralin derivatives of Formula I using, for example, as starting materials 3-amino-indan-5-ol or 6-methoxy-1-aminoindan. Methods of preparation of the starting materials are also disclosed. 6-Methoxy-indan-1-ylamine is prepared by conversion of 6-methoxy-indan-1-one to 6-methoxy-indan-1-one oxime followed by reduction to 6-methoxy-indan-1-ylamine. Alternatively 6-methoxy-1-aminoindan can be prepared by reductive amination (NaCNBH3 and NH4OAc) of 6-methoxy-indan-1-one to 6-methoxy-indan-1-ylamine. 3-Amino-indan-5-ol can be prepared by using a Friedel-Crafts acylation of an N-protected 3-aminoindan, followed by a Baeyer-Villiger oxidation with subsequent hydrolysis.
These methods for producing starting materials such as 3-amino-indan-5-ol and 6-methoxy-indan-1-ylamine are accompanied by low yields and low reproducibility. Thus, there is a need for reliable processes to produce indanylamine and aminotetralin derivatives in high yields as intermediates to prepare compounds of Formula I, wherein the processes are suitable for industrial production.